Spontaneous release of interleukin 1 from human blood monocytes reflects bone formation in idiopathic osteoporosis.

Abstract

Osteoporosis is a state of reduced skeletal mass characterized by various rates of bone remodeling. Multiple locally elaborated factors have been identified that appear to influence the cellular events in bone remodeling. The possible role(s) of these factors in the pathogenesis of osteoporosis is unknown. One such factor, interleukin 1 (IL-1), is of particular interest, as this protein is known to stimulate bone resorption and perhaps formation. Consequently, we have measured the spontaneous secretion of IL-1 activity by cultured peripheral blood monocytes obtained from 22 osteoporotic patients and 14 age-matched control subjects. Monocytes from osteoporotic patients produced more IL-1 than did monocytes from control subjects. When patients were grouped according to monocyte-produced IL-1 activity, dynamic parameters of bone formation, as judged by quantitative histomorphometric analysis of iliac crest bone biopsies and by circulating levels of bone 4-carboxyglutamic acid protein (BGP)-a marker of bone formation-were higher in subjects with elevated IL-1 activity; whereas, indices of bone resorption and static indices of bone formation were similar in subjects with either high or normal IL-1 activity. IL-1 activity released by peripheral blood monocytes appears to reflect bone formation rate in osteoporotic patients and may be of pathogenetic significance in a subset of individuals with osteoporosis.Primary osteoporosis is an extremely common condition in which inadequate accumulation of bone tissue during maturation or excessive loss thereafter (or both) culminates in a clearly subnormal level of bone mass (1). Among its clinical forms are senile osteoporosis attributable to the undefined impact ofaging on bone remodeling, postmenopausal osteoporosis reflecting excessive bone loss due to estrogen (and perhaps progestin) withdrawal, and idiopathic osteoporosis, a poorly understood acceleration of bone loss occurring in young men and premenopausal women (2). In each case, the insufficiency of bone mass is visualized as stemming from a remodeling disturbance in which bone resorption exceeds formation.The various clinical forms of primary osteoporosis also exhibit histological heterogeneity, as disclosed by quantitative histomorphometric studies with bone biopsies (3). Subsets of these osteoporotic populations exhibit "high-turnover" disease, characterized by accelerated rates of remodeling. At the other end of the spectrum are patients with "low-turnover" osteoporosis characterized by low rates of remodeling (4). High-turnover osteoporosis is of special interest because it could stem from an abnormality of one or more of the factors known to activate bone remodeling. However, studies have failed to incriminate significant differences in systemically elaborated remodeling stimulators, including parathyroid hormone, calcitonin, calcitriol (1a,25-dihydroxyvitamin D3), and insulin-like growth factor 1 (5-7).Evidence has accumulated that suggests that cells of the monocyte-macrophage series may serve as local ...

IL-1β Inhibits Human Osteoblast Migration

“…In idiopathic osteoporosis patients, IL-1β release by peripheral blood monocytes, precursors of osteoclasts, was shown to be increased significantly when compared with healthy individuals (21,22). The notion of IL-1-mediated bone loss also is supported by a study where inhibition of IL-1 with soluble IL-1R was shown to significantly reduce inflammation, loss of connective tissue and bone resorption in the periodontium of Macaca fascicularis primates infected with pathogens (23).…”

“…The importance of IL-1β for bone loss during inflammatory diseases has been shown in various studies as explained before (21)(22)(23). The most prominent function of IL-1β in bone loss is the capacity to activate osteoclastogenesis (25)(26)(27).…”

Gene Expression Profiling in Bone Tissue of Osteoporotic Mice

“…the histamine synthesis enzyme), and GCR (glucocorticoid receptor) were upregulated in circulating monocytes of subjects with low BMD (6). In addition, increased production of IL-1 and tumour necrosis factor α (TNF-α) has been observed in circulating mononuclear cells in women with postmenopausal osteoporosis (7,8).…”

A distinctive role of the leukotriene B 4 receptor BLT1 in osteoclastic activity during bone loss

“…Estrogen withdrawal after ovariectomy or natural menopause is associated with increased production of TNF-␣ and IL-1 (37,38), both of which increase LTB 4 production in neutrophils (44) and macrophages (45). LPS was also reported to increase LTB 4 production in both cell types (46,47).…”